A Study to Determine the Safety and the Efficacy of Fasinumab Compared to Placebo and Naproxen for Treatment of Adults With Pain From Osteoarthritis of the Knee or Hip

NCT ID: NCT03161093

Last Updated: 2022-11-14

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 3307 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-08-17
• Study Completion Date: 2021-08-27

Brief Summary

The primary objective of the study is to evaluate the efficacy of fasinumab compared with placebo, when administered for up to 16 weeks in patients with pain due to osteoarthritis (OA) of the knee or hip.

The secondary objectives of the study are:

1. To evaluate the efficacy of fasinumab compared with naproxen, when administered for up to 16 weeks in patients with pain due to OA of the knee or hip

2. To evaluate the efficacy of fasinumab compared with placebo, when administered for up to 44 weeks in patients with pain due to OA of the knee or hip

3. To assess the safety and tolerability of fasinumab compared with naproxen, when administered for up to 16 weeks in patients with pain due to OA of the knee or hip

4. To assess the safety and tolerability of fasinumab compared with naproxen, when administered for up to 52 weeks in patients with pain due to OA of the knee or hip

5. To assess the safety and tolerability of fasinumab compared with naproxen, when administered for up to 104 weeks in patients with pain due to OA of the knee or hip

6. To evaluate the pharmacokinetic (PK) profile of fasinumab administered to patients with pain due to OA of the knee or hip for up to 52 weeks

7. To evaluate the PK profile of fasimumab administered to patients with pain due to OA of the knee or hip for up to 104 weeks

8. To evaluate the immunogenicity of fasinumab administered to patients with pain due to OA of the knee or hip for up to 52 weeks

9. To evaluate the immunogenicity of fasinumab administered to patients with pain due to OA of the knee or hip for up to 104 weeks

10. To evaluate the efficacy of fasinumab compared with naproxen, when administered for up to 44 weeks in patients with pain due to OA of the knee or hip

Conditions

Osteoarthritis, Knee; Osteoarthritis, Hip

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

Fasinumab dosing regimen 1

Fasinumab Subcutaneous (SC) dosing regimen 1 and naproxen-matching placebo oral

Group Type: EXPERIMENTAL

Fasinumab

Intervention Type: DRUG

Solution for injection in pre-filled syringe

Naproxen-matching placebo

Intervention Type: DRUG

Capsule

Fasinumab dosing regimen 2

Fasinumab SC dosing regimen 2 and naproxen-matching placebo oral

Group Type: EXPERIMENTAL

Fasinumab

Intervention Type: DRUG

Solution for injection in pre-filled syringe

Naproxen-matching placebo

Intervention Type: DRUG

Capsule

Fasinumab-matching placebo and naproxen

Group Type: EXPERIMENTAL

Naproxen

Intervention Type: DRUG

Pharmaceutical form: Capsule

Fasinumab-matching placebo

Intervention Type: DRUG

Solution for injection in pre-filled syringe

Fasinumab-matching placebo and naproxen-matching placebo

Group Type: EXPERIMENTAL

Fasinumab-matching placebo

Intervention Type: DRUG

Solution for injection in pre-filled syringe

Naproxen-matching placebo

Intervention Type: DRUG

Capsule

Interventions

Fasinumab

Solution for injection in pre-filled syringe

Intervention Type: DRUG

Naproxen

Pharmaceutical form: Capsule

Intervention Type: DRUG

Fasinumab-matching placebo

Solution for injection in pre-filled syringe

Intervention Type: DRUG

Naproxen-matching placebo

Capsule

Intervention Type: DRUG

Other Intervention Names

REGN475

Eligibility Criteria

Inclusion Criteria

Year 1:

1. Male and female patients, at least 18 years of age, at screening

2. A clinical diagnosis of OA of the knee or hip based on the American College of Rheumatology criteria with radiologic evidence of OA (K-L score ≥2 for the index joint) at the screening visit

3. Moderate to severe pain in the index joint defined at both the screening and randomization visits

4. Willing to discontinue current pain medications and to adhere to study requirements for rescue treatments (acetaminophen/paracetamol) to be taken as needed with a maximum daily dose of 2500 mg (countries where 500 mg strength tablets/capsules are available) or 2600 mg (countries where 325 mg strength tablets/capsules are available)

5. A history of at least 12 weeks of analgesics use for pain due to OA of the knee or hip, as defined by:

1. Inadequate pain relief from acetaminophen/paracetamol AND

2. Intolerance to or inadequate pain relief from opioid or tramadol therapy, unwillingness to take opioid or tramadol therapy for a medically acceptable reason, or lack of access to an opioid or to tramadol

6. Currently using a stable dose of NSAID.

7. Willing to discontinue glucosamine sulfate and chondroitin sulfate treatments during the initial 16 weeks of treatment

8. Stable treatment with glucosamine sulfate and chondroitin sulfate treatments must be stopped during the pre-randomization period

9. Consent to allow all radiographs and medical/surgical/hospitalization records of care received elsewhere prior to and during the study period to be shared with the investigator

10. Willing to maintain current activity and exercise levels throughout the study

11. Willing and able to comply with clinic visits and study-related procedures and willing to provide follow-up information related to any JR surgery that occurs within the period of time covered by their intended participation in the study

12. Able to understand and complete study-related questionnaires

Year 2:

Note: Any Year 1 patient attending their week 52 visit on or after 26 March 2020 will no longer have the option to enroll into Year 2.

1. Completed the treatment period of Year 1

2. Did not permanently discontinue study drug during Year 1

3. Received no less than 10 of the 13 planned doses of SC study drug during the treatment period of Year 1

4. Provide informed consent for Year 2

5. Willing to continue to maintain current activity and exercise levels throughout Year 2

Exclusion Criteria

1. Non-compliance with the Numeric Rating Scale (NRS) recording during the pre-randomization period

2. History or presence at the screening visit of non-OA inflammatory joint disease, Paget's disease of the spine, pelvis or femur, neuropathic disorders, multiple sclerosis, fibromyalgia, tumors or infections of the spinal cord, or renal osteodystrophy

3. History or presence on imaging of arthropathy, neuropathic joint arthropathy, hip or knee dislocation, extensive subchondral cysts, significant bone collapse or bone loss, or pathologic fractures

4. Trauma to the index joint within 3 months prior to the screening visit

5. Signs or symptoms of carpal tunnel syndrome within 6 months of screening

6. Patient is not a candidate for MRI

7. Is scheduled for a JR surgery to be performed during the study period or who would be unwilling or unable to undergo JR surgery if needed

8. History or presence at the screening visit of autonomic or diabetic neuropathy, or other peripheral neuropathy, including reflex sympathetic dystrophy

9. History or diagnosis of chronic autonomic failure syndrome including pure autonomic failure, multiple system atrophy

10. History of naproxen intolerance, or existence of a medical condition that is high risk for naproxen-associated complications

11. Resting heart rate of <50 beats per minute (bpm) or >100 bpm at the screening or randomization visits

12. History or presence of 2nd or 3rd degree heart block, 1st degree heart block with abnormal Complex of Q, R, and S waves on an electrocardiogram (QRS) complex, or bifascicular block by ECG assessment at the screening visit

13. History or presence of orthostatic hypotension at the screening, prerandomization, or randomization visits

14. History of poorly controlled hypertension

15. Use of systemic corticosteroid within 30 days prior to the screening visit. Intra-articular corticosteroids in the index joint within 12 weeks prior to the screening visit, or to any other joint within 30 days prior to the screening visit

16. Exposure to an anti-Nerve growth factor (NGF) antibody prior to the screening visit or known sensitivity or intolerance to anti-NGF antibodies

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Teva Pharmaceutical Industries, Ltd.

INDUSTRY

Sponsor Role: collaborator

Regeneron Pharmaceuticals

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Clinical Trial Management

Role: STUDY_DIRECTOR

Regeneron Pharmaceuticals

Locations

Arizona Arthritis & Rheumatology Research, PLLC

Mesa, Arizona, United States

Arizona Research Center

Phoenix, Arizona, United States

Tucson Orthopaedic Research Center

Tucson, Arizona, United States

Baptist Health Center for Clinical Research

Little Rock, Arkansas, United States

Medvin Clinical Research

Covina, California, United States

TriWest Research Associates, LLC

El Cajon, California, United States

BioSolutions Clinical Research

La Mesa, California, United States

Pacific Arthritis Care Center

Los Angeles, California, United States

Artemis Institute for Clinical Research

San Diego, California, United States

Artemis Clinical Research

San Marcos, California, United States

Lynn Institute of Denver

Aurora, Colorado, United States

Lynn Institute of the Rockies

Colorado Springs, Colorado, United States

Panorama Orthopedics & Spine Center

Golden, Colorado, United States

Arthritis and Rheumatic Disease Specialties

Aventura, Florida, United States

Jacksonville Center for Clinical Research

Jacksonville, Florida, United States

Clinical Neuroscience Solutions, Inc.

Jacksonville, Florida, United States

Sensible Healthcare

Ocoee, Florida, United States

Clinical Neuroscience Solutions, Inc.

Orlando, Florida, United States

Jewett Orthopaedic Clinic

Orlando, Florida, United States

Lovelace Scientific Resources

Venice, Florida, United States

Meridian Clinical Research

Savannah, Georgia, United States

Advanced Clinical Research

Meridian, Idaho, United States

Medex Healthcare Research, Inc.

Chicago, Illinois, United States

Northwestern University

Chicago, Illinois, United States

Healthcare Research Network II, LLC

Flossmoor, Illinois, United States

Integrated Clinical Trial Services, Inc.

West Des Moines, Iowa, United States

Klein & Associates, MD PA

Cumberland, Maryland, United States

Klein & Associates, MD, PA

Hagerstown, Maryland, United States

The Center for Rheumatology and Bone Research

Wheaton, Maryland, United States

Clinical Pharmacology Study Group

Worcester, Massachusetts, United States

The Center for Pharmaceutical Research

Kansas City, Missouri, United States

Medex Healthcare Research, Inc.

St Louis, Missouri, United States

Sundance Clinical Research, LLC

St Louis, Missouri, United States

Physician Research Collaboration, LLC

Lincoln, Nebraska, United States

Lovelace Scientific Resources, Inc.

Albuquerque, New Mexico, United States

United Medical Associates

Binghamton, New York, United States

Regional Clinical Research, Inc.

Endwell, New York, United States

Medex Healthcare Research

New York, New York, United States

Buffalo Rheumatology and Medicine, PLLC

Orchard Park, New York, United States

Orchard Park Family Practice

Orchard Park, New York, United States

PMG Research of Raleigh, LLC d/b/a PMG Research of Cary

Cary, North Carolina, United States

DJL Clinical Research, PLLC

Charlotte, North Carolina, United States

Hickory Family Practice Associates

Hickory, North Carolina, United States

Peters Medical Research LLC

High Point, North Carolina, United States

PMG Research of Salisbury, LLC

Salisbury, North Carolina, United States

PMG Research of Winston-Salem, LLC

Winston-Salem, North Carolina, United States

Sterling Research Group, Ltd.

Cincinnati, Ohio, United States

Hillcrest Clinical Research

Oklahoma City, Oklahoma, United States

Altoona Center for Clinical Research

Duncansville, Pennsylvania, United States

Low Country Rheumatology, PA

Charleston, South Carolina, United States

PMG Research of Charleston, LLC

Mt. Pleasant, South Carolina, United States

Clinical Research Solutions

Franklin, Tennessee, United States

PMG Research of Knoxville

Knoxville, Tennessee, United States

Clinical Neuroscience Solutions, Inc.

Memphis, Tennessee, United States

Pioneer Research Solutions, Inc.

Cypress, Texas, United States

Southwest Rheumatology Research, LLC

Mesquite, Texas, United States

Center for Arthritis and Rheumatic Diseases

Chesapeake, Virginia, United States

Rheumatology & Pulmonary Clinic

Beckley, West Virginia, United States

CCBR Vejle

Vejle, , Denmark

Synexus Clinical Research GmbH

Leipzig, Saxony, Germany

Synexus Clinical Research GmbH

Berlin, , Germany

Synexus Clinical Research GmbH

Bochum, , Germany

Synexus Clinical Research GmbH

Frankfurt, , Germany

Qualiclinic Kft.

Budapest, , Hungary

Synexus Magyarorszag Kft

Budapest, , Hungary

Synexus Magyarorszag Kft.

Debrecen, , Hungary

Synexus Magyarorszag Kft.

Gyula, , Hungary

BKS Research Kft.

Hatvan, , Hungary

Hevizgyogyfurdo es Szent Andraes ReumaKorhaz

Hévíz, , Hungary

Szabolcs-Szatmar-Bereg Megyei Korhazak es Egyetemi Oktato Korhazak Josa Andras Oktatokorhaza Klinikai Kutatasi Osztaly

Nyíregyháza, , Hungary

Synexus Magyarorszag Egeszsegugyi Kft.

Zalaegerszeg, , Hungary

Hospital of Lithuanian University of Health Sciences Kaunas Clinics

Kaunas, , Lithuania

Saules Seimos Medicinos Centras, Jsc

Kaunas, , Lithuania

Republican Panevezys Hospital

Panevezys, , Lithuania

Center Outpation Clinic, Public Institution

Vilnius, , Lithuania

Synexus Polska Sp. z o.o Oddzial w Poznaniu

Poznan, Greater Poland Voivodeship, Poland

Krakowskie Centrum Medyczne Sp. z o.o.

Krakow, Lesser Poland Voivodeship, Poland

Synexus Polska Sp. z o.o. Oddzial we Wroclawiu

Wroclaw, Lower Silesian Voivodeship, Poland

MCBK Sc lwona Czajkowska Monika Barney

Grodzisk Mazowiecki, Masovian Voivodeship, Poland

Synexus Polska Sp. z o.o. Oddzial w Warszawie

Warsaw, Masovian Voivodeship, Poland

Specjalistyczny Osrodek Medycyny Wieku Dojrzalego Sp. z o.o.

Warsaw, Masovian Voivodeship, Poland

Synexus Polska Sp. z o.o. Oddzial w Gdansku

Gdynia, Pomeranian Voivodeship, Poland

Synexus Polska Sp. z o.o. Oddzial w Gdyni

Gdynia, Pomeranian Voivodeship, Poland

ClinicMed Daniluk, Nowak Sp.j.

Bialystok, , Poland

Synexus Polska Sp. z o.o. Oddzial w Katowicach

Katowice, , Poland

Malopolskie Centrum Kliniczne

Krakow, , Poland

CLINMEDICA RESEARCH OMC, Spolka z Ograniczona Odpowiedzialnoscia Spolka Komandytowa

Skierniewice, , Poland

Etg Zgierz

Zgierz, , Poland

Specjalistyczny Osrodek Medycyny Wieku Dojrzalego Sp. z o.o. Jednostka 02 - SOMED - Lodzkie Centrum Osteoporozy

Lodz, Łódź Voivodeship, Poland

Clinica Medicala Synexus Ltd.

Bucharest, , Romania

SC Policlinica CCBR SRL

Bucharest, , Romania

"SBEIHPE ""Kazan State Medical University"" of MHSD of Russia"

Kazan', Tatarstan Republic, Russia

"CDCR ""Healthy Joints"" L.L.C."

Novosibirsk, , Russia

City Out-Patient Clinic #109

Saint Petersburg, , Russia

Samara Regional Clinical Hospital n.a.V.D.Seredavin

Samara, , Russia

"State Autonomous Healthcare Institution of Yaroslavl Oblast ""Clinical Hospital #3"""

Yaroslavl, , Russia

Tread Research-Tygerberg Hospital

Parow, Cape Town, South Africa

Welkom Clinical trial Centre

Welkom, Free State, South Africa

Wits Clinical Research

Johannesburg, Gauteng, South Africa

University of Pretoria

Pretoria, Gauteng, South Africa

Global Clinical Trials

Pretoria, Gauteng, South Africa

Synexus SA Stanza Clinical Research Centre

Pretoria, Gauteng, South Africa

Synexus Watermeyer Clinical Research Centre

Pretoria, Gauteng, South Africa

Roodepoort Medicross Clinical Research Centre

Roodepoort, Gauteng, South Africa

Soweto Clinical Trials Centre (CTC)

Soweto, Johannesburg, South Africa

Synapta Clinical Research Center

Durban, KwaZulu-Natal, South Africa

Enhancing Care

Durban, KwaZulu-Natal, South Africa

Aliwal Shoal Medical Centre

eMkhomazi, KwaZulu-Natal, South Africa

Mzansi Ethical Research Centre Middleburg

Middelburg, Mpumalanga, South Africa

Langeberg Medicross Medical Centre

Kraaifontein, Western Cape, South Africa

Paarl Research Centre

Paarl, Western Cape, South Africa

Synexus Helderberg Clinical Trial Centre

Somerset West, Western Cape, South Africa

TASK Applied Science

Cape Town, , South Africa

Mzansi Ethical Research Centre Cape Town

Cape Town, , South Africa

Newtown Clinical Research

Johannesburg, , South Africa

CETA Leganes

Leganés, Madrid, Spain

Complejo Hospitalario Universitario A Coruna

A Coruña, , Spain

MeDiNova Investigacion y Desarrollo

Madrid, , Spain

Centro De Investigacion Clinica En Enfermedades Cronicas - Cicec

Santiago de Compostela, , Spain

Clínica Nuevas Tecnologias en Diabetes y Endocrinologia (NTDE)

Seville, , Spain

Hospital Quiron Salud Infanta Luisa

Seville, , Spain

"Municipal Establishment ""Cherkasy Regional Hospital of Cherkasy Oblast Council"""

Cherkasy, , Ukraine

Kharkiv City Multispecialty Hospital #18

Kharkiv, , Ukraine

Medical center of Private High Educational Institute Institute of General Practice-Family Medicine

Kyiv, , Ukraine

"Subsidiary Company ""Medical Research and Practice Center Medbud of the Public Joint Stock ""Holding Company ""Kyivmiskbud"""

Kyiv, , Ukraine

"Kyiv Railway Clinical Hospital No.2 of branch ""Health Center "" of the PJSC ""Ukrainian Railway"""

Kyiv, , Ukraine

Lviv Regional Hospital for veterans of the war and former political prisoners

Lviv, , Ukraine

Synexus Thames Valley Clinical Research Centre

Reading, Berkshire, United Kingdom

Synexus Scotland Clinical Research Centre

Glasgow, Lanarkshire, United Kingdom

Synexus Lancashire Clinical Research Centre

Chorley, Lancashire, United Kingdom

MediNova North London Dedicated Research Centre, Mount Vernon Hospital

Northwood, Middlesex, United Kingdom

Synexus North East Clinical Research Centre - Hexham General Hospital

Hexham, Northumberland, United Kingdom

Synexus Midlands Clinical Research Centre

Birmingham, West Midlands, United Kingdom

Synexus Wales Clinical Research Centre

Cardiff, , United Kingdom

Synexus Merseyside Clinical Research Centre

Liverpool, , United Kingdom

Synexus Manchester Clinical Research Centre-Manchester Science Park

Manchester, , United Kingdom

Medinova Research East London Clinical Studies Centre

Romford, , United Kingdom

MeDiNova Research Yorkshire Clinical Studies Centre

Shipley, , United Kingdom

MediNova South London Dedicated Research Centre

Sidcup, , United Kingdom

Countries

United States; Denmark; Germany; Hungary; Lithuania; Poland; Romania; Russia; South Africa; Spain; Ukraine; United Kingdom

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

2016-005020-29

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

R475-OA-1611

Identifier Type: -

Identifier Source: org_study_id